rs2839471

Positions:

• chr21-42134346-C-T
• chr21-42134346-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001004416.3(UMODL1):​c.3776-3093C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 152,126 control chromosomes in the GnomAD database, including 11,779 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.39 (11779 hom., cov: 33)
• Consequence: UMODL1 NM_001004416.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.106

Genes affected

UMODL1 (HGNC:12560): (uromodulin like 1) Predicted to be an extracellular matrix structural constituent. Predicted to be involved in neutrophil migration. Predicted to act upstream of or within several processes, including adipose tissue development; cellular response to gonadotropin-releasing hormone; and regulation of ovarian follicle development. Predicted to be located in cytoplasm and external side of plasma membrane. Predicted to be integral component of membrane. Predicted to be active in apical plasma membrane; cell surface; and extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

UMODL1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.492 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UMODL1	NM_001004416.3	c.3776-3093C>T		intron_variant		ENST00000408910.7	NP_001004416.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UMODL1	ENST00000408910.7	c.3776-3093C>T		intron_variant		1	NM_001004416.3	ENSP00000386147.2

Frequencies

GnomAD3 genomes AF: 0.389 AC: 59067 AN: 152008 Hom.: 11774 Cov.: 33

Gnomad AFR AF: 0.322

Gnomad AMI AF: 0.353

Gnomad AMR AF: 0.406

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.509

Gnomad SAS AF: 0.395

Gnomad FIN AF: 0.377

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.419

Gnomad OTH AF: 0.407

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.388 AC: 59097 AN: 152126 Hom.: 11779 Cov.: 33 AF XY: 0.388 AC XY: 28877 AN XY: 74340

Gnomad4 AFR AF: 0.321

Gnomad4 AMR AF: 0.406

Gnomad4 ASJ AF: 0.349

Gnomad4 EAS AF: 0.508

Gnomad4 SAS AF: 0.397

Gnomad4 FIN AF: 0.377

Gnomad4 NFE AF: 0.419

Gnomad4 OTH AF: 0.409

Alfa AF: 0.416 Hom.: 19594

Bravo AF: 0.387

Asia WGS AF: 0.426 AC: 1480 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	5.2
DANN	Benign	0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2839471; hg19: chr21-43554456;